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Cardiac optogenetics

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1 Author(s)
Abilez, O.J. ; Bio-X Program, Stanford Univ., Stanford, CA, USA

For therapies based on human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) to be effective, arrhythmias must be avoided. Towards achieving this goal, light-activated channelrhodopsin-2 (ChR2), a cation channel activated with 480 nm light, and a first generation halorhodopsin (NpHR1.0), an anion pump activated by 580 nm light, have been introduced into hiPSC. By using in vitro approaches, hiPSC-CM are able to be optogenetically activated and inhibited. ChR2 and NpHR1.0 are stably transduced into undifferentiated hiPSC via a lentiviral vector. Via directed differentiation, both wildtype hiPSC-CM (hiPSCWT-CM) and hiPSCChR2/NpHR-CM are produced and subjected to both electrical and optical stimulation. Both hiPSCWT-CM and hiPSCChR2/NpHR-CM respond to traditional electrical stimulation and produce similar contractility features but only hiPSCChR2/NpHR-CM can be synchronized and inhibited by optical stimulation. Here it is shown that light sensitive proteins can enable in vitro optical control of hiPSC-CM. For future therapy, in vivo optical stimulation could allow precise and specific synchronization of implanted hiPSC-CM with patient cardiac rates and rhythms.

Published in:

Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE

Date of Conference:

Aug. 28 2012-Sept. 1 2012